Newsgroups: alt.drugs.chemistry
From: [e--u--s] at [netcom.com] (Eleusis)
Subject: The Methylamine FAQ v2.0 - new & delicious
Date: Sun, 21 Jan 1996 15:55:05 GMT
The Methylamine FAQ v2.0
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Table of Contents
-----------------
1) Introduction/What's New?
2) Questions/Answers
3) Making Methylamine via Hofmann Rearrangement (Hypohalite version)
4) Making Methylamine via Schmidt Rearrangement
5) Making Methylamine HCl via Formaldehyde
6) Making Acetamide from Acetic Acid & Urea
7) Making Acetamide from Ethyl Acetate & Ammonia
8) Making Absolute Ethanol
This document deals with the preparation of Methylamine and Methylamine
Hydrochloride from non-restricted precursors. Both of these compounds
are currently extremely difficult to purchase legitimately or otherwise.
This is the third major version of the FAQ, and in this version I am
adding more physical data on the syntheses as well as a new reaction
called the Schmidt Rearrangement which might be more attractive to some.
Also, the astute observer will notice I changed the ratios of reactants
in the Hofmann as well as scaling it down by 5 times. This is the result
of empirical testing to better accomodate the person with small scale
glassware (like myself).
Please note that I am not a chemist by trade, but I *have* taken great
pains to insure the accuracy of all information, including empirical
testing. While this means I am not an authoritative reference, it also
means that a non-chemist can put this information to use.
What's New? v1.5: I have tested many variations on the Hofmann process
in order to make it more efficient and easier. In my empirical testing,
I have come up with several process improvements that make life with
Hofmann so much easier and much more efficient to boot. For one thing, I
have sucessfully performed it without having to use any ice in the
reactants, reducing the volume of reactants by over 50% (and less volume
is less one has to distill to get the good stuff). Yield hasn't suffered
at all, and though slightly more time is required to perform the first
step, distillation has been effectively doubled in speed (good for those
of us with 500mL flasks and such to work with). Also, I added a new
process that some may find more convenient called the Schmidt Reaction.
It is very similar to the Hofmann, but please note that I haven't tested
it nearly so much. Perhaps in a future "final touch" version I will put
more empirical data into it.
What's New? v2.0: I must warn against selecting the Schmidt reaction to
make the product, as my experiences it with it have been less than
pleasant. Do try to use a fume hood of some sort if you wish to pursue
this otherwise highly attractive method. Also, I have re-written the
Formalin/Ammonium Chloride method with a more practical view in mind.
This new write-up makes it much more worthy of consideration - live and
learn, eh? In addition, I have added another preparation of Acetamide
which uses all OTC (well, except for the Calcium Oxide) reagents and
is both cheap and easy.
Questions/Answers
Q1) What is Methylamine or Methylamine Hydrochloride?
A1) Methylamine, or more correctly Monomethylamine, is of formula CH3NH2,
a simple primary amine. It is a noxious, acrid gas which is quite nasty
and a tad on the explosive side. For this reason, it is usually sold or
prepared as it's hydrochloride salt, or as an aqueous solution of about
40% concentration. The HCl salt is in the form of white deliquescent
crystals, and is frequently substitutable for the aq. soln. in many
synthesis preparations.
Q2) What is this lovely compound used for?
A2) Methylamine/HCl has a number of uses in which it is impossible or
highly impractical to substitute. Several examples are:
Methylamination of Hydroquinone to result in the ring structure
p-methylaminophenol, the Sulfate of which is the photographic developing
agent Metol.
Aqueous Methylamine (40%) is used to prepare animal hides for taxidermy,
especially when it is vital to preserve the hair.
Synthesis of complex ring structures via the Mannich Condensation in
conjunction with an aldehyde and a ketone.
And, of course, it is a necessary for the preparation of several drugs
(both legal and otherwise).
Q3) Where can I get it?
A3) You can't unless you happen to be in an industry that uses it or are
prepared to sign your privacy away to the DEA. That's why this FAQ exists;
so you can make it yourself. Besides, if you can't make it with the data
provided in here, you have no business messing with it anyway.
Q4) What are the legal implications of having it?
A4) Well, it is required by any chemical supply institution that they
take down all sorts of data on anyone attempting to purchase a kilogram
or more of either the aqueous solution or the salt, but it has been my
experience that *no* place will sell it to an individual in any quantity.
I even have a friend who owns his own photography business and he says
he couldn't buy any as well. I could go off on a long pedantic spiel
about how ridiculous this is, but why bother. Possession of Methylamine
is not a felony, in any amount, though you may violate some hazardous
waste and/or zoning rules above a certain quantity. It's not the kind of
thing you want to store next to your bed, anyway. If you have it in
conjunction with other compounds, such as P-2-P or MDP-2-P, then if for
some reason the DEA came a'knockin', you could be prosecuted for
Conspiracy to Manufacture Amphetamines, which could be damaging to your
lifestyle and health (see Code of Federal Regulations 21 for more info).
Q5) Can I make it?
A5) Definitely. If you have half a clue and some reasonable grasp of
chemistry fundamentals, you can make a good chunk of methylamine in
an afternoon. I am covering three individual processes in this FAQ that
I feel are relatively easy but, primarily, because they give good yields.
The ones I cover are:
Hofmann Rearrangement of an Amide to an Amine
Schmidt Rearrangement of a Carboxylic Acid/Anhydride to an Amine
Aldehyde to Amine
Also, it is possible to make it from completely over the counter materials
if one chooses the Hofmann rearrangement and synthesizes the Acetamide
from Urea and glacial Acetic Acid (synthesis included as well). And as a
free bonus, I am including the most common preparation of Anhydrous
(Absolute) Ethanol from grain alcohol or denatured alcohol.
Finally, I would be remiss if I did not mention that there are several
other processes for producing amines, though I have not treated them.
Some other processes to consider among the hundreds are:
Methyl Chloride + Ammonia in an ether solution (CH3NH2 + NH4Cl)
CH3OH + NH3 at 300C
CH3NO2 (Zn/HCl) -> CH3NH2*HCl
etc...
For further reference, consult these references:
Organic Reactions vol. 3
Vogel's Practical Organic Chemistry
Organic Syntheses, vol. 1
On to the syntheses...
* * *
3) Synthesis of Methylamine/Methylamine HCl via Hofmann Rearrangement
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There are two approaches to producing an amine from an amide using the
Hofmann rearrangement reaction. One way is to react the primary amide
with an alkaline-halide solution (eg - Sodium Hydroxide and Bromine).
The other method is to use an alkaline-hypohalite solution (eg - Sodium
Hydroxide and Calcium Hypochlorite). The astute observer will notice
that there is *no* chemical difference in the two processes. One
produces the Hypohalite in situ, the other uses the Hypohalite itself.
Substitution of various halogens/halides/hypohalites/hydroxides is
acceptable, but I feel I have picked the best combination of maximal
yield and ease of availability. Feel free to prove me wrong ;-). Also,
at least one text specifies that Sodium Hypochlorite produces much higher
yields than Sodium Hypobromite. This delicious vindication is expected
since Chlorine is a more reactive halogen than Bromine. Now, we are going
to use Calcium Hypochlorite, in the form of powdered pool shock, because
concentrated Sodium Hypochlorite is a rare, unstable creature indeed. Our
yield will not suffer in the slightest because of this.
The main example presented will be the alkaline-hypohalite method as it
is the easiest to acquire the necessary chemicals. It is of interest to
note that the alkaline-halide method is much easier to perform, process-
wise, in that it is more forgiving of sloppy technique.
The general theory behind the process is that the hypohalite will convert
the amide to a haloamide. This then spontaneously changes to the
isocyanate when heated and decomposes to the amine from the water present.
In effect, all that happens is that a Carbonyl (CO) group is stripped off
the starting amide to yield the corresponding amine. Yields pre-
purification are around 80%, post-purification average around 65%.
Certain uses of the resulting amine will not require purification,
though, so it will be left up to you whether or not to perform those
steps.
To make methylamine we start with Acetamide. The general, unbalanced
reaction process is thus:
CH3CONH2 + Ca(OCl)2 ----> (CH3CONCl)2Ca++ + H2O then
(CH3CONCl)2Ca++ + NaOH ----> CH3NH2 + Na2CO3
*CAUTION* Methylamine is a poisonous, noxious inflammable gas. It has a
strong ammonia/rotting fish-like odor. It's not as bad as
Chlorine gas, though, which can be produced if one is careless
in the beginning!
You can scale these reactions up or down within reason. What is
reasonable? I can't say, but I have done batches from .01 to 1 mole with
no difficulty. The key problems in scaling this reaction have to do with
heat gradients in the flask and inadequate stirring. Use your own
judgement, keeping in mind that this is *not* an industrial process.
One reference to keep in mind (Thanks to J.W. Smith for sending this one)
concerns the first step of the reaction.
Whitmore and Thorpe, J. of the Amer. Chemical Society, Vol 63, April
1941, p1118
"It was necessary to allow several hours for the formation of the
N-chloroamide before heating to degradation temperature. With this
modification it was possible to prepare methylamine...consistently in
78% yield."
In my experience, this is a *true* statement. Please remember to keep
the reactants well iced, though. Now, to begin:
In a large mixing bowl which can contain a smaller stainless steel
mixing bowl, prepare an ice bath with water and salt to bring the
temperature down to -10C or so. Setup your glassware for simple
distillation with magnetic stirring beforehand because certain steps
need to be performed quickly. Use a vacuum adapter to connect to the
receiver flask, and attach some rubber or polypropylene tubing to the
vaccum nipple to connect to a bubbler setup (a funnel inverted in a
beaker, or a plastic aquarium aerator tube). The distilling flask should
be sitting in in a stainless steel bowl with nothing in it (you will add
pre-heated oil to the bowl).
*NOTE* In order to make this as painless as possible, please observe the
following recommendations: 1) Keep the mixing bowl temperature as
close to 0C or less as possible; 2) Keep the Hypochlorite solution
as it is being added as close to 0C or less as possible; 3) After
half the Hypochlorite solution has been added, place a plastic bag
with 50-100g ice/salt/water mix into the bowl to help keep
temperatures low (use this instead of directly adding ice to the
reactants, which adds a considerable volume of water making the
process less volumetrically efficient); 4) Purchase an 8lb bag of
ice ahead of time!
Next you will prepare three solutions.
10g of Acetamide in 20mL of distilled water.
16.4g of Calcium Hypochlorite (Pool shock) in 50mL of hot distilled water
24g of Sodium Hydroxide (Lye) in 40mL of cold distilled water
This last solution should be prepared slowly as it is quite exothermic.
Set all three aside in a freezer. Now prepare the mixing apparatus which
will be a stainless steel "mixing bowl" suspended in the ice/salt bath
made earlier. We use a stainless steel bowl here so that heat transfer
will be maximal, while preventing any corrosive interaction. A glass
bowl will not be sufficient for larger scale preparations as it will not
conduct heat fast enough to prevent the reactants from going over 10C (at
which point the Haloamide will decompose and you'll have to start over).
Take the Sodium Hydroxide solution out of the freezer once it is cool,
but not cold.
After the bowl has been sitting in the ice bath for a few minutes, add
the Acetamide solution. Stir well until the solution has cooled to -10C.
Now, *slowly* add the Hypochlorite solution to the mixing bowl in bursts
of no more than a couple mL while stirring vigorously. If you do this
perfectly, there will be no fizzing or bubbling at all. This depends on
how cold you keep the mixture, and how slowly you add the pool shock!
Realistically, the considerable heat evolution of the reaction will make
adding the last few mL a trying task! Keep an additional 50g of ice on
hand to throw directly into the mixture if necessary. This solution *may*
evolve Chlorine gas so you should obviously perform this step under a
fume hood or outside). Keep stirring until it has calmed down and turned
a turbid colorless to light green Let it sit for 2 hours, stirring
occasionally and making sure that it never gets warmer than 5C.
After the 2 hours is up, add the Sodium Hydroxide solution quickly with
stirring. The solution should immediately turn a chalky, milk white.
That's because a lot of Sodium Carbonate just got generated. You no
longer need be concerned over it's temperature, so you can leave the
solution in this state overnight if perhaps the hours have passed by too
quickly and you've suddenly realized it's 2:00am.
Preheat a water bath on the stove (or wherever) to about 80C and place
the stainless steel mixing bowl in it. Once the temperature of the
solution hits about 65C, take the bowl out and set aside while stirring
all the while. This is where it rearranges, and the reaction is
exothermic enough to sustain it's temperature nicely. If you find the
temperature climbing past 80C, immerse the bowl into some cold water
briefly. After about 15 minutes the temperature will start to fall, at
which point you should transfer the whole mess to the distilling flask.
Before you continue you need to choose whether you want to make the
hydrochloride salt or the aqueous solution of Methylamine, though.
Heat the flask using an oil bath to 100C after adding this solution to
effect gentle boiling which will drive off the Methylamine as a gas.
In my experience, misbehavior is likely to occur at this point. One
particular problem to watch out for is the sucking back of bubbler
solution (be it plain water or 6N HCl) into the receiver flask. I don't
know why the pressure in the distilling flask would go below atmospheric,
and therefore cause this to happen, but it has several times with me.
Needless to say, this results in a serious mess and *botches* the whole
process (I have found a cure for this by using an automotive one-way
vacuum valve, like a PCV).
Continue heating the flask contents until you have collected around
100mL of distillate in the receiver.
For the aqueous solution: Place 18mL of cool distilled water into your
bubbler setup. The *expected*, not theoretical, yield of Methylamine
from this amount of reactants is 7 grams. I have used a plastic aquarium
aerator tube as the bubbler with excellent results. Sure beats using an
inverted funnel.
For the HCl salt: Do exactly as above except use 6N Hydrochloric Acid.
6N HCl may be produced by diluting 60.4mL of "Muriatic Acid" to 100mL
with distilled water. Evaporate the bubbler solution to dryness then add
15ml of water, 10mL 10% NaOH soln. and heat gently to a boil with
constant motion until dense white fumes appear. This will remove the
Ammonium Chloride. Remove from heat while stirring as it cools down.
Pulverize the dry residue, then reflux with absolute Ethanol for several
minutes. Filter the refluxed soln. on a heated Buchner or Hirsch funnel,
then distill the alcohol off the filtrate until crystals just begin to
form. Allow the soln. to cool naturally to room temperature, then cool
further in an ice bath. Filter the solution on a chilled Buchner funnel
with suction. The yield of Methylamine Hydrochloride should be around
55% of the theoretical.
To clean the white residue off of your glassware, dump some muriatic
acid straight from the jug onto them and swirl.
References:
Journal of Chemical Education, v14, pg542
Organic Reactions volume 3
Vogels Elementary Practical Organic Chemistry, pg574
4) Methylamine/Methylamine HCl via Schmidt Rearrangement
--------------------------------------------------------
This reaction is quite similar to the Hofmann Rearrangement, but it
reacts a Carboxylic Acid with Hydrazoic Acid to generate the desired
amine. Like the Hofmann, it has wide application and versatility, yet
also has excellent yields in many cases. It will also preserve the
chirality of the starting Acid/Anhydride, which is not of interest to
us, but an important fact to note. The restrictions on this process
are that the starting Carboxylic Acid must not adversely react with
either Sulfuric Acid or Hydrazoic Acid. It would be a crime if I didn't
also mention that the Schmidt Rearrangement has much greater application
than just making amines from carboxylics, but that is well beyond the
scope of this FAQ. See Organic Reactions v3 for more details.
To make Methylamine or the HCl salt using the Schmidt Rearrangement,
you start off with glacial Acetic Acid. You might be saying to yourself,
"Damn, why bother with the Hofmann!" since glacial Acetic Acid is so
easy to get, but, there is a drawback... And that is Hydrazoic Acid,
which is *not* easy to get. As well, Hydrazoic Acid is extrememly
poisonous and should not be handled without a fume hood under *any*
circumstances. Really. This is coming from a guy who has no problem
distilling Ether solutions in his kitchen, so take it seriously. Why
bother, then? Well, because you *can* generate the Hydrazoic Acid in situ
using Sodium Azide and conc. Sulfuric Acid. I have not personally tried
this because I don't have a powder addition funnel. Anyway, Sodium Azide
is not too hard to come by through chemical supply houses and Sulfuric
Acid is easy to acquire in the form of Instant Power Drain Opener. This
reaction MUST be performed in an area of adequate upward ventilation, or
at least with the air flowing away from you.
*NOTE* In the initial testing of any undesireable interaction between
Sodium Azide, Acetic Acid and Sulfuric Acid, I mixed 5mL of each
into a small cup underneath my "fume hood". Though I smelled
*nothing*, within seconds my head felt like it was expanding, my
heart started racing, and I felt more weak and confused than
normal. I just barely escaped and recovered in 15 minutes, but,
Needless to say, this procedure is a *tad* on the dangerous side.
You have been *warned*.
Theory behind this reaction is:
R-COOH + NaN3 ---H2SO4---> intermediates ---H2O---> R-NH2 + CO2
The intermediates in making amines are isocyanates (O==C==N) just like
the Hofmann Rearrangement. The isocyanates are decomposed with water,
just like the Hofmann. In fact, there is a lot of similarity between
the Hofmann and the Schmidt reactions. Before I detail the synthesis
steps, I should note that if you wish to generate the Hydrazoic Acid
in the flask by adding Sodium Azide, you might need a powder addition
funnel. This bit of equipment is quite pricey and it's likely you won't
have one, so the first part of the synthesis details how to make the
Hydrazoic Acid separately.
There are three variations on this process you may choose from:
1) Add Hydrazoic Acid to a Carboxylic Acid/Benzene or Chloroform
mixture (O.React. claims this is the preferred method).
2) Add Sulfuric Acid to Carboxylic Acid/Hydrazoic Acid/Benzene or
Chloroform mixture (this is my prefered method).
3) Add Carboxylic Acid/Hydrazoic Acid/Benzene or Chloroform mixture
to Sulfuric Acid or Sulfuric Acid/Benzene or Chloroform mixture.
a) Preparation of Hydrazoic Acid
*CAUTION* This compound is EXTREMELY EXPLOSIVE and HIGHLY TOXIC! I am
not exaggerating! Do not, under ANY circumstances, allow the
acid to heat above room temperature (bp: 37C). Use latex
gloves to handle, and dispose of small quantities using
plenty of water followed by dilute baking soda/water.
Prepare a paste out of 65g Sodium Azide (1m NaN3) and 65mL of water in
a beaker. Add 400mL of either Chloroform or Benzene to this paste
(depending on what you have available, but be consistent later on) and
stir well. Dump this mixture into a round bottom flask situated in an
ice/salt bath, drop in a stirrer magnet, attach a Claisen adapter,
addition funnel, and thermometer. Let this mixture cool to 0C.
Place 49g of cold concentrated Sulfuric Acid into the addition funnel,
but only after you make sure the stopcock is turned OFF. Ever so slowly
add the acid to the flask, dropwise, such that the flask contents stay
around 1C, and never go over 5C. This might take a while, be patient.
After all is added, pour the flask contents into a separatory funnel
(ventilation is absolutely required here) and separate out the aqueous
layer. Your HN3 is dissolved in the Chloroform/Benzene layer. If you
wish to determine the exact concentration of the acid, you may titrate
it, but the reaction generally goes to completion with no secondary
hydrazides forming as long as you kept the temperature where I told you
to. Some HN3 might have gone to the aqueous layer, but mostly the
resulting Sodium Sulfate will crowd it out. The resulting concentration,
then, is the moles of Hydrazoic Acid over the the total moles of HN3 and
your solvent (Chloroform = 117g/m, Benzene = 78g/m).
b) Making the Amine (All Variations)
Setup your glassware for simple distillation with a claisen adapter,
three way adapter, pressure-equalized addition funnel, water cooled
condenser, vacuum adapter and receiver flask to catch any condensed
solvent vapors.
c) Specifics for Variation 2
Drop your stirrer magnet into the flask and add 250mL of Benzene or
Chloroform (take your pick), Next, add .25 moles glacial Acetic Acid
(15g) then .5 moles Hydrazoic Acid with stirring. Warm this solution to
about 40C using a water bath. Make sure all joints are air tight. Add
20mL concentrated Sulfuric Acid very slowly. The reaction is mildly
exothermic, so take care and watch the temperature. The reaction finishes
within 2 hours. The amine is in the sulfate salt form. To convert to the
hydrochloride salt form, first add an equinormal amount of 10% NaOH
solution and stir well. Next, extract the free amine with ether and
bubble HCl gas through it to precipitate out the crystals. Filter to
recover.
5) Methylamine HCl from Formaldehyde and Ammmonium Chloride
-----------------------------------------------------------
This is the least desirable of all three processes. The yields are
lower than the two rearrangements, and it requires substantial labor
to get a decently pure product. Not "labor" as in difficult but
"labor" as in a lot of it. I would suggest this only for those who
have a large supply of Formaldehyde available to them (note - N.
Coffey found formaldehyde at Home Depot - look for "Mildewcide" and
dissolve it in enough water to make a 37% solution to depolymerize
the paraformaldehyde).
Place 250g of Ammonium Chloride and 500g of technical Formaldehyde
(37%, Formalin). Rig the flask for simple distillation such that a
thermometer extends into the reaction mixture, and a Liebig or West
condenser. Heat the mixture on the steam bath until no more
distillate comes over, then turn up the heat and hold the reaction
temperature at 104C until, once again, nothing else comes over. This
should take from 4 to 5 hours. The distillate may contain interesting
things, so check out footnote 1 for details on what to do with it.
Next, the reaction flask should be cooled rapidly to room temperature
by immersion into first a warm water bath (60C) swirled, and then an
ice bath. Filter the solution on the vacuum Buchner funnel to recover
~62g of Ammonium Chloride crystals. Concentrate the filtrate using
moderate vacuum and gentle heat until the volume is reduced to half.
Filter the mother liquor once again after cooling quickly to yield
a second batch of Ammonium Chloride, ~19g.
Transfer the filtrate to a ceramic evaporating dish and heat on a
water bath until a crystalline scum forms on the top. Cool the
dish quickly then filter the mess on the vacuum Buchner to yield
~96g of Methylamine Hydrochloride. Concentrate the filtrate once
again to obtain a second crop of crystals, ~18g. Concentrate the
filtrate a third time as far as possible using the water bath, then
store the dish in a vacuum dessicator loaded with Sodium Hydroxide
in the bottom for 24 hours. Add Chloroform to the residue left in
the crucible to dissolve out Dimethylamine Hydrochloride (distill
off the Chloroform to recover - good stuff) then filter on the
venerable old vacuum Buchner funnel to yield an additional ~20g of
Methylamine Hydrochloride, washing the crystals in the funnel with
a small portion of Chloroform (~10mL).
Purification of the Methylamine HCl is in order now, so transfer
all of the crude product to a 500mL flask and add either 250mL of
absolute Ethanol (see end of FAQ for preparing this) or, ideally,
n-Butyl Alcohol (see Footnote 4). Heat at reflux with a Calcium
Chloride guard tube for 30 minutes. Allow the undissolved solids to
settle (Ammonium Chloride) then decant the clear solution and cool
quickly to precipitate out Methylamine HCl. Filter rapidly on the
vacuum Buchner funnel and transfer crystals to a dessicator (see
Footnote 3). Repeat the reflux-settle-cool-filter process four
more times if using absolute Ethanol, or two more times if using
n-Butyl Alcohol. The yield of Methylamine HCl should be 100g.
Footnote 1 - The byproducts of the first step are Dimethoxymethane
and Sodium Formate.
Footnote 2 - The Methylamine solutions in all steps should be cooled
rapidly to promote smaller crystal formation.
Footnote 3 - According to the original document, centrifuging is the
most satisfactory method of drying products because of their
hygroscopic nature. I suggest warming in an oven on a glass dish then
transfering to a vacuum dessicator loaded with either concentrated
Sulfuric Acid or Sodium Hydroxide in the bottom. It is not normally
necessary to have absolutely dry Methylamine HCl anyway.
Footnote 4 - The solubility of Ammonium Chloride in absolute Ethanol
is 0.6g/100g at 15C. The solubility in n-Butyl Alcohol is neglible,
even at its boiling point. If you use n-Butyl Alcohol, you will only
need to perform 3 reflux/filter operations to obtain sufficiently pure
Methylamine Hydrochloride.
References to this section:
Sharp & Solomon, J. Chem. Soc. 1477 (1931)
Werner, J. Chem. Soc. 850 (1917)
Sommelet, Compt. rend. 178, 217 (1924)
Hofmann, Ann. 79, 16 (1851)
6) Synthesis of Acetamide from Acetic Acid and Urea
---------------------------------------------------
Urea is conveniently obtained as a constituent of many fertilizers
and so it is easily obtained. Sources have indicated that a 50lb bag
can be purchased for $15 in the US. It is of less than ideal purity
from this source, so some washing will be in order (with what?).
Glacial Acetic Acid is easily obtained from photographic supply
stores in high purity and for cheap as well. This reaction produces
Acetamide with such purity that the product does not even need to be
recrystallized (the reaction goes to completion with no side products).
The reaction is:
CH3COOH + NH2CONH2 ----> CH3CONH2 + CO2 + 2NH3
Place 125g Urea and 125g of Acetic Acid in a 500mL round bottom flask
in preparation for simple refluxing with magnetic stirring and without
cooling water (or use cooling water heated to about 80C). Attach
condenser, claisen adapter and place thermometer so that the bulb is
around 1cm from the bottom, fully immersed. Heat on the mantle gently
to bring the temperature of the mixture to 150C in 20 minutes. The
mixture should be refluxing in the condenser, and probably subliming
in it as well unless heated "cooling" water is used. Push any crystals
back down as necessary. Hold at reflux until the temperature rises to
195-200C (approximately 1.5 hours) Allow to cool, then rearrange the
condenser for distilling (its really preferable to use 80C water in the
condenser). Heat to collect nearly pure Acetamide starting at 200C with
most coming over from 214-216C. If the product smells strongly of mice
(as in the rodents), then recrystallization from warm methanol is in
order. To recrystallize, take 50g of Acetamide, dissolve in 40mL warm
Methanol, add 100mL Ether to crash it out and allow to stand. If no
crystals have formed after an hour or so, gently scratch the inside of
the beaker with a glass rod. If your product is only faintly odorous
and is colourless to white, then it is considered pure. Melting point
is 80.5C.
7) Synthesis of Acetamide from Ethyl Acetate and Ammonia
--------------------------------------------------------
Ethyl Acetate is allowed to mix with concentrated Ammonia solution
for several days to make Acetamide. This is a very attractive method
because all the reagents involved are easy to acquire and cheap.
a) Preparation of Ethyl Acetate from Ethanol and glacial Acetic Acid
Dehydrate at least 100mL of grain alcohol to yield absolute Ethanol.
74mL (58g) will be required. Add this quantity of Ethanol to a round
bottom flask with 225g glacial Acetic Acid and 3g of concentrated
Sulfuric Acid. Heat at reflux on an electric heating mantle for 12
hours then attach a Vigreaux or Hempel fractionating column to
distill off the crude ester at 76-77C. Change receiver flasks and
recover the excess of Acetic Acid, bp 118C. Wash the first receiver
contents with a half volume of saturated Sodium Bicarbonate solution
then add 50g of anhydrous Sodium Sulfate (the salt of Sulfuric Acid
and Sodium Hydroxide, dried in an oven at >100C for several hours)
and distill the pure dry ester once again. Yield should be greater
than 70g.
b) Reaction of Ethyl Acetate and Ammonia to make Acetamide
Add 44g of Ethyl Acetate and 90mL of concentrated Ammonia solution
(~28%) to a 500mL round bottom flask with a stirrer magnet. Plug
the neck with a thermometer in a thermometer adapter and stir
gently for 48 hours or until the mixture becomes homogenous (stop
the stirrer occasionally to check). Attach standard distillation
apparatus but leave off the receiver flask at first, connecting a
short piece of rubber tubing to the receiver adapter which is
submerged in a beaker of dilute HCl (10-20%). Heat gently on a
mantle to drive off the excess ammonia into the beaker. When no
more bubbles come over then attach the receiver flask and commence
distilling acetamide from 170C up, rapidly. Run 80C water though
the condenser to prevent clogging. Once distillation slows to a
crawl, remove the receiver flask and set aside in a hot water
bath (80-90C). Clean up the glassware used for the distillation
then use the receiver flask as the distilling flask and a glass
container with screw-lid top as a receiver. Run 80C water through
the condenser as before, and redistill the Acetamide, which
should come over completely at 216C using the heating mantle.
Yield should be greater than 24g.
8) Preparation of Absolute Ethanol from Grain Alcohol
-----------------------------------------------------
Absolute, or 99.5% water-free, Ethanol is frequently necessary in
many organic operations. It is quite easy to prepare from the
azeotrope with water such as "Everclear" brand grain alcohol,
"moonshine" or "Rectified Spirits" (an old term for the same
thing).
Dehydrate 75g of fresh anhydrous Calcium Oxide in a vacuum
dessicator for 24 hours (a bit redundant, I know) or heat in an
oven at 200C for 2 hours, then immediately transfer to the vacuum
dessicator until use. Setup glassware for simple refluxing with a
water-cooled condenser and a Calcium Chloride guard tube. Place
350mL of Ethanol into the flask, quickly add the Calcium Oxide
and hold at gentle reflux on the water bath or heating mantle for
6 hours. Allow the mixture to stand overnight, then distill off
the alcohol, discarding the first few mL (it may be more convenient
to just vent the condenser to the atmosphere for the first couple
of minutes after distillation has commenced). Yield should be
better than 315mL. Store the absolute Ethanol in a tightly closed
glass container as it will pick up water from the air rapidly.
- [e--u--s] at [netcom.com] - The Methylamine FAQ v2.0 - 01/21/96 -
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. <[e--u--s] at [netcom.com]> - Finger me for my PGP Key .
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. /o\ Give me lava lamps or give me death... /o\ .
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